We plan to investigate the endocrine mechanisms involved in the control of growth and differentiation of melanoma cells in tissue culture. We are interested in delineating the biochemical pathways involved in the cyclic cAMP-mediated induction of tyrosinase in these cells. We intend to determine (1) the kinetics involved in the MSH stimulated rise in tyrosinase; (2) the cellular target sites for cyclic AMP; (3) the importance of such target interactions to the hormonal response and; (4) what transcriptional and translational events are required for the endocrine-induced phenotypic (melanogenic) response. In addition to MSH, the following other hormones or chemical messengers known to exert physiological effects on several cell types will be studied for their effects on melanoma cell growth and differentiation: steroid hormones (estradiol, testosterone, cortisol, cortisone, corticosterone, and vitamin D3), thyroid (T3 and T4) hormones, pituitary growth hormone and prolactin, indoleamines, parathormone, calcitonin, somatostatin, glucagon, insulin, and nerve growth factor. Since numerous cell systems require calcium for regulating the cellular response to hormonal stimulation, the role of calcium ions in mediating the action of MSH will be investigated. Finally, structure-activity requirements for MSH action on melanoma cells will be investigated using MSH peptides and related structures prepared by organic synthesis.